The objective of this proposal is to investigate the mechanisms in control of hepatobiliary function. Kepone, mirex, and photomirex are close structural analogs of chlorinated hydrocarbone compounds of known toxic effects on the liver. These will be used as tools to induce impairment of hepatobiliary function using model compounds for biliary excretion. Previous studies using isolated perfused liver preparations and intact animal preparations have indicated that, although all three chemicals are potent inducers of hepatic mixed function oxidases, they suppress the biliary excretion of anionic model compounds. Neither metabolism nor the rate of bile secretion appear to be related to this chlorocarbon induced hepatic dysfunction. Aberration of hepatocellular energetics which does accompany hepatobiliary dysfunction by the above compounds may be causally related to the disrupted hepatic function. While all three compounds are capable of inducing hepatic dysfunction, only Kepone is extremely potent in potentiating CCl4 hepatotoxicity which is manifested as totally disrupted hepatic function and hepatocellular necrosis at very low, individually ineffective levels. Studies proposed herein will further examine chemical induced hepatobiliary dysfunction with emphasis on the underlying mechanisms aimed at understanding of the basic physiological and biochemical events in control of hepatobiliary function.